The present invention, in some embodiments thereof, relates to methods and kits for determining predisposition to develop kidney diseases, and, more particularly, but not exclusively, to methods of designing life style change and treatment regimens for a subject predisposed to develop a kidney disease.
Chronic Kidney Disease (CKD) is a powerful independent risk factor for cardiovascular disease and death at all stages. Most patients with CKD will succumb to cardiovascular complications rather than reach end-stage kidney disease (ESKD). Recent reports estimate that as many as 600 million people worldwide have CKD, and hence are at greatly increased risk of cardiovascular disease including hypertension [Hypertext Transfer Protocol(dot)worldwideweb (dot)kidney(dot)org(dot)au/NewsEvents/WorldKidneyDay/tabid/655/Default (dot)aspx].
Based on information from those countries where renal replacement therapy is available and registries are maintained, there are close to one million people with ESKD receiving dialysis treatment or a kidney transplant. In the United States, an estimated 15.5 million have stage 3 and 4 CKD, and 584,000 have ESKD. African Americans have five times greater risk for kidney disease than European Americans. Correspondingly, African-Americans also have a higher risk of mortality from cardiovascular disease than Americans of European ancestry, including death, non-fatal myocardial infarction, and stroke. Finally, it is now appreciated that hypertension, once thought to be a leading cause of CKD leading to ESKD, is the consequence of primary renal glomerular disease in certain risk populations.
Mapping by admixture linkage disequilibrium (MALD) localized an interval on chromosome 22, in a region that includes the MYH9 gene, which was shown to contain African ancestry risk variants associated with certain forms of ESKD (Kao et al. 2008; Kopp et al. 2008). This led to the new designation of MYH9 associated nephropathies. Subsequent studies identified clusters of single nucleotide polymorphisms (SNPs) within MYH9 with the largest odds ratios (OR) reported to date for the association of common variants with common disease risk (Bostrom and Freedman 2010). These MYH9 association studies were extended to earlier stage and related kidney disease phenotypes, and to population groups with varying degrees of recent African ancestry admixture (Behar et al. 2010; Nelson et al. 2010). Thus, the MYH9 has been proposed as a major genetic risk locus for a spectrum of non-diabetic ESKD. However, despite intensive efforts including re-sequencing of the MYH9 gene no suggested functional mutation has been identified (Nelson et al. 2010).
U.S. Patent Application No. 20100297660 to Winkler Cheryl et al. (“SINGLE NUCLEOTIDE POLYMORPHISMS ASSOCIATED WITH RENAL DISEASE”) discloses methods for determining the genetic predisposition of a human subject to developing renal disease, such as focal segmental glomerulosclerosis (FSGS) or end-stage kidney disease by detection of one or more haplotype blocks comprising at least two tag single nucleotide polymorphisms (SNPs) in a non-coding region of a MYH9 gene or detecting the presence of at least one tag SNP in a non-coding region of a MYH9 gene.
Additional background art includes Tzur S, et al. (Missense mutations in the APOL1 gene are highly associated with end stage kidney disease risk previously attributed to the MYH9 gene) Hum. Genet. 2010, 128:345-50; Rosset S, et al. (The population genetics of chronic kidney disease: insights from the MYH9-APOL1 locus) Nat. Rev. Nephrol. 2011, May 3. [Epub ahead of print]; Genovese G, et al. (Association of trypanolytic ApoL1 variants with kidney disease in African Americans) Science 2010; 329:841-5; Behar D M, et al. (African ancestry allelic variation at the MYH9 gene contributes to increased susceptibility to non-diabetic end-stage kidney disease in Hispanic Americans) Hum. Mol. Genet. 2010 19(9):1816-27; Shlush L I, et al. (Admixture mapping of end stage kidney disease genetic susceptibility using estimated mutual information ancestry informative markers) BMC Med Genomics. 2010 3:47; and U.S. Patent Application No. 20110030078.